In keeping with the irony of PD-1, being originally named for its supposed function as an inducer of programmed death, the bona fide TRAIL–TRAIL-R and CD95L–CD95 death receptor–ligand systems may turn out to serve as alternative, possibly additional immune checkpoint systems whose inhibition may prove essential to extend the ICB concept beyond the conventional ICBs, importantly, also to KRAS-mutated cancer. Here, TNFSF10 is linked to cancer.